Stereochemistry and Mechanism of the Brønsted Acid Catalyzed Intramolecular Hydrofunctionalization of an Unactivated Cyclic Alkene

Abstract

Through employment of deuterium-labelled substrates, the triflic acid-catalyzed intramolecular exo-addition of the X–H(D) (X = N, O) bond of a sulfonamide, alcohol, or carboxylic acid across the C=C bond of a pendant cyclohexene moiety was found to occur, in each case, with exclusive formation (≥90%) of the anti-addition product without loss or scrambling of deuterium as determined by 1H and 2H NMR spectroscopy and MS analysis. Kinetic analysis of triflic acid-catalyzed intramolecular hydroamination of N-(2-cyclohex-2'-enyl-2,2-diphenylethyl)-p-toluenesulfonamide (1a) established the second-order rate law: rate = k2[HOTf][1a] and the activation parameters: ΔH‡ = 9.7 ± 0.5 kcal mol−1 and ΔS‡ = −35 ± 5 cal K−1 mol−1. An inverse α-secondary kinetic isotope effect of kD/kH = 1.15 ± 0.03 was observed upon deuteration of the C2' position of 1a, consistent with partial C–N bond formation in the highest energy transition state of catalytic hydroamination. The results of these studies were consistent with a mechanism for the intramolecular hydroamination of 1a involving concerted, intermolecular proton transfer from an N-protonated sulfonamide to the alkenyl C3' position of 1a coupled with intramolecular anti-addition of the pendant sulfonamide nitrogen atom to the alkenyl C2' position.

Gold(I)-Catalyzed Intramolecular Hydroamination of Unactivated Terminal and Internal Alkenes with 2-Pyridones

“…However, whereas numerous systems catalyze the intramolecular hydroamination of terminal alkenes, the intramolecular hydroamination of aliphatic 1,2-disubstituted alkenes remains problematic . Extant approaches catalyzed by early transition metal complexes, lanthanide metallocene complexes, late transition metal complexes, or Brønsted or Lewis acids as well as uncatalyzed Cope-type hydroamination suffer from a number of limitations including narrow substrate scope, poor functional group compatibility, and the necessity of sterically biasing gem -2,2-disubstitution. Recently, the intramolecular hydroamination of aliphatic 1,2-disubstituted alkenes has been realized via proton-coupled electron transfer or electrocatalytic generation of amidyl radicals, but these methods are restricted to N -arylcarboxamide derivatives. − Herein, we report a gold­(I)-catalyzed method for the intramolecular hydroamination of 6-alkenyl-2-pyridones that is effective for aliphatic 1,2-disubstituted alkenes.…”

Stereoselective Organocatalytic Alkylations with Carbenium Ions

“…The formation of an ether byproduct is often observed in S N 1-type reactions of alcohols. In addition, the process is reversible 59 and the ether can release the alcohol and the carbenium ion.…”

Bismuth(iii) triflate promoted intramolecular hydroamination of unactivated alkenyl sulfonamides in the preparation of pyrrolidines

“…To test such an option, 14 we treated the reaction mixture 15 with the proton scavenger (1,8-bis(dimethylamino)naphthalene, Proton Sponge®) with variable stoichiometry relative to Bi (OTf ) 3 . The addition of equimolar ratio(s) of base to the catalyst (0.2 and/or 0.3 eq.)…”